Process for the preparation of cyclohexanol derivatives

ABSTRACT

A process for the preparation of 4-tert-butyl-cyclohexanol, comprising the hydrogenation of 4-tert-butyl-phenol or of 4-tert-butyl-cyclohexanone in the presence of a catalytic system composed of rhodium on a Al 2  O 3 , SiO 2 , TiO 2 , SiO 2 .Al 2  O 3  or charcoal support, in combination with HBF 4  or BF 3 .[Y] n  wherein Y designates a R 2  O group, R being a C 1  to C 6  lower alkyl radical, or a CH 3  CO 2  H, H 3  PO 4  or H 2  O group and index n is equal to zero, 1 or 2.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to a process for the preparation of4-tert-butyl-cyclohexanol essentially in the form of its cis isomer,which process comprises the hydrogenation of 4-tert-butyl-phenol or of4-tert-butyl-cyclohexanone in the presence of a catalytic systemcomposed of rhodium on a Al₂ O₃, SiO₂, TiO₂, SiO₂.Al₂ O₃ or charcoalsupport, in combination with HBF₄ or BF₃.[Y]_(n) wherein Y designates aR₂ O group, R being a C₁ to C₆ lower alkyl radical, or a CH₃ CO₂ H, H₃PO₄ or H₂ O group and index n is equal to zero, 1 or 2.

The invention further provides a catalytic system composed of rhodium ona Al₂ O₃, SiO₂, TiO₂, SiO₂.Al₂ O₃ or charcoal support, in combinationwith HBF₄ or BF₃.[Y]_(n) wherein Y designates a R₂ O group, R being a C₁to C₆ lower alkyl radical, or a CH₃ CO₂ H, H₃ PO₄ or H₂ O group andindex n is equal to zero, 1 or 2.

BACKGROUND OF THE INVENTION

The present invention relates to the perfume industry. Moreparticularly, it concerns a new process for the preparation of4-tert-butyl-cyclohexanol essentially in the form of its cis isomer.This compound is useful in the fragrance industry, particularly as anintermediate product for the preparation of esters, namely acetic ester.

Specifically, 4-tert-butyl-cyclohexyl acetate is a well-known perfumingingredient, which is available on the market under several tradenames.It is generally commercialized in the form of an isomeric mixturewherein the cyclanic cis isomer is present in varied proportions, moreoften in an amount between 30 and 65% by weight. Now, it has beenestablished that there is a fundamental difference between the olfactivequality of this cis isomer and that of the corresponding trans isomer,the first of these compounds being preferred [see Arctander, Perfume andFlavor Chemicals, Montclair, N.J. (1969), sects. 440 and 441]. For thisreason, a great number of research groups have directed their effortstowards the preparation of said ester in its preferred isomeric form.Nevertheless, the problem of the availability of a product rich in thecis isomer remains of actuality. As a matter of fact, while some of thenumerous syntheses disclosed in the prior art provide isomeric mixtureswith an adequate content in cis isomer, this is only achieved at thecost of expensive technical solutions which render their industrialexploitation not very profitable.

U.S. Pat. No. 2,927,127, granted on Mar. 1, 1960, describes a processfor the preparation of a cis/trans mixture of 4-tert-butyl-cyclohexylacetate having a content in cis isomer as high as 87.5%, which processconsists in the catalytic hydrogenation of p-tert-butyl-phenol in thepresence of Rh on an active charcoal support and in the acetylation, bymeans of acetic anhydride, of the product thus obtained. Thehydrogenation step is carried out at a high pressure, of the order of7×10⁶ Pa.

Likewise, in Chemical Abstracts, vol. 80, sec. 14700s, there isdisclosed a process for reducing p-tert-butyl-phenol by means of acatalytic hydrogenation with Rh on active charcoal or with rutheniumdioxide, at a pressure of 10×10⁶ Pa. The reported content in cis isomerwas 64.1%.

U.S. Pat. No. 4,343,955 teaches a process for the preparation ofp-tert-butyl-cyclohexanol by catalytic hydrogenation in the presence ofruthenium on alumina, at a pressure of 4×10⁶ Pa and a temperature of100° C. In this case, the content of the resulting product in cis isomerwas 74.8%.

Finally, European Patent No. 141,054 describes a two-step processcomprising the reduction of p-tert-butyl-phenol by means of palladium onalumina, at 120°-180° C. and a pressure above 20×10⁶ Pa, followed by thehydrogenation of the resulting product in the presence of ruthenium onsame alumina support, at a temperature of 70°-200° C. and under the samepressure conditions. The cis isomer was present in the obtained mixturein an amount of the order of 46%.

As described, the prior art processes resorted to methods requestingdrastic reaction conditions, thus creating technical problems of aparticular nature when such methods are applied at an industrial scale.On the other hand, it is well-known that amongst the questions to beconsidered when applying industrially a process which uses heterogeneouscatalysis, lies that of the feasibility of recycling the catalyst, aswell as the concern for its lifetime and reactivation. All these factorsenter into account when determining the worth of a process from aneconomical point of view and are, as a result, critical factors whensaid process is put into industrial application.

It has now been discovered that, henceforth, it is possible to obtainisomeric mixtures of 4-tert-butyl-cyclohexanol which are rich in the cisisomer, through a process that, in addition, presents clear advantagesover the prior art methods in what concerns the recycling of thecatalyst. Although this process comprises the catalytic hydrogenation of4-tert-butyl-phenol or of 4-tert-butyl-cyclohexanone in the presence ofa rhodium-based catalyst, it allows nevertheless the application of mildreaction conditions. It has in fact been observed that the use of acatalyst composed of rhodium previously deposited on an alumina supportin the presence of a co-catalyst such as boron trifluoride, not onlymade it possible to obtain an excellent stereoselectivity, but alsoprovided a catalytic system the activity of which remained constant andadequate over a high number of operations, thus rendering the processmore cost-effective. While the use of fluorinated catalysts of the typeBF₃.Al₂ O₃ has been described in the context of alkylation reactionsinvolving aromatic systems and KF.Al₂ O₃ has been reported as a catalystin simple addition-type reactions [see J. Chem. Soc. 1986, 1133-39] ,there are few reports of the use of such catalysts in hydrogenationreactions and, to the best of our knowledge, their use in thestereoselective hydrogenation of cyclohexanones or phenols, to yieldcyclohexanols, has never been suggested. As a co-catalyst, BF₃ may beemployed as such or in the form of one of its complexes.

THE INVENTION

The object of the present invention is, therefore, to provide a processfor the preparation of 4-tert-butyl-cyclohexanol essentially in the formof its cis isomer, which process comprises the hydrogenation of4-tert-butyl-phenol or of 4-tert-butyl-cyclohexanone in the presence ofa catalytic system composed of rhodium on a Al₂ O₃, SiO₂, TiO₂, SiO₂.Al₂O₃ or charcoal support, in combination with HBF₄ or BF₃.[Y]_(n) whereinY designates a R₂ O group, R being a C₁ to C₆ lower alkyl radical, or aCH₃ CO₂ H, H₃ PO₄ or H₂ O group and index n is equal to zero, 1 or 2.

The reaction which characterizes this process is schematicallyillustrated as follows: ##STR1##

Although the hydrogenation reaction may be carried out at atmosphericpressure, it was observed that the best yields, as well as the mostfavorable isomeric distribution, were obtained when pressures of theorder of 3×10⁵ Pa to around 2×10⁶ Pa were applied.

The temperature was not a critical factor. As a result of the use of thenew catalytic system, the reaction can be carried out at temperaturesclose to room temperature. According to a preferred embodiment of theprocess of the invention, good final product yields are obtained whentemperatures of the order of 25° to 200° C. are used, and 40°-130° C.are typical temperature values, adapted to most practical cases.

The conversion rates observed were excellent and reached 100% in manycases, while the good steroselectivity of the catalytic system usedfinds expression in the production of isomeric mixtures of4-tert-butyl-cyclohexanol whose content in the preferred cis isomer canreach around 90% by weight.

Under the reaction conditions defined above, the reaction times are ofthe order of a few hours. In many cases, 2 to 5 hours are enough toachieve almost complete conversion of the starting phenol orcyclohexanone.

Without wanting to speculate on the real structure of the catalyticsystem employed, it is apparent that the use of a "co-catalyst" such asBF₃ resulted in a modification of the nature of the surface of thealumina support, thus imparting thereto a stoichiometry which can bebetter defined as [Al₂ O₃ ]₀.8.[AlF₃ ]₀.2. Typically, catalysts composedof 5% by weight of rhodium on Al₂ O₃ were used. These are commonconcentration values for commercially available grades of Rh/Al₂ O₃.

One of the critical parameters in ensuring that the reaction is carriedout in good conditions is the ratio of relative proportions of BF₃ andrhodium. I have been able to establish that this ratio, defined in molarquantities, could be comprised between about 0.5 and 15; however, Iobserved that an increase in the proportion of BF₃ led to the formationof undesirable side-products. Finally, the amount of catalyst, definedin terms of the molar quantity of rhodium versus the molar quantity ofphenols or cyclohexanols, could be of the order of 0.1-0.5%.

The hydrogenation takes place in an organic solvent inert under thereaction conditions and, to this end, it is convenient to use an ether,for example tetrahydrofuran, or an aliphatic or cycloaliphatichydrocarbon such as, for example, cyclohexane.

The specific and preferred catalyst used in the process according to theinvention, which is also an object of the latter, can be convenientlyprepared by impregnation of Rh/Al₂ O₃. Thus, a mixture of BF₃.O(C₂ H₅)₂,or trifluoroboroetherate, with Rh/Al₂ O₃ in ethyl acetate, was kept ataround 45° C. under argon for 75 min, and the solid product wassubsequently isolated and dried. Before its use, the catalyst thusobtained is maintained under inert gas atmosphere. It was observed that,when treated in this manner, the catalyst maintained its specificactivity for 7 days at least. Although the catalytic system thusprepared is perfectly adapted to all practical use of concern, otherefficient systems can be obtained by simply adding the co-catalyst toRh/Al₂ O₃ or Rh/C. Thus, tetrafluoroboric acid can be directly added tothe reaction mixture upon hydrogenation in the presence of rhodium onalumina or on charcoal. Such a system shows a stereospecificity which isfully comparable to that of the above-described previously impregnatedcatalyst.

The invention will now be described in greater detail by way of thefollowing examples, wherein the temperatures are indicated in degreescentigrade and the abbreviations have the usual meaning in the art.

EXAMPLE 1 Preparation of the Catalyst

General method by impregnation

A. 10 g of 5% (parts by weight) rhodium on a commercial alumina supportequivalent to 0.50 g or 4.86 mmole, 0.920 ml of BF₃.O(C₂ H₅)₂ [distilledbefore use; 7.48 mmole] and 60 ml of ethyl acetate were charged into a100 ml flask under nitrogen. After mixing, the flask was stirred bymeans of a rotating evaporator at 45° and around 9.3×10⁴ Pa for 75 min,then the mixture was concentrated until dry. A solid product was thusobtained which was kept under argon until used.

B. 3 g of 5% (parts by weight) rhodium on a TiO₂ support, 0.276 ml ofBF₃.O(C₂ H₅)₂ [distilled before use] and 18 ml of ethyl acetate wereintroduced into a reactor under argon. The resulting mixture was keptunder mild stirring for about 1 h 15 at 45° by means of a rotatingevaporator. It was then concentrated to dryness. The catalyst obtainedin this manner was kept under argon until used.

Preparation of 4-Tert-Butyl-Cyclohexanol

A mixture consisting of 50 g (0.33 mole) of 4-tert-butyl-phenol, 1.35 gof the catalyst prepared as described above under example 1A and 100 gof cyclohexane was introduced in an autoclave under nitrogen and thenhydrogen was introduced until a stable pressure around 16×10⁵ Pa hadbeen established. The reaction mixture was then heated to about 98° andthe reaction was followed by gas chromatography.

After 135 min, the reaction was interrupted by cooling to around 45° andthe autoclave was purged with a nitrogen flow. After filtering, thecatalyst was recovered under a flow of argon, washed with cyclohexaneand recycled for the following hydrogenation operations.

4-tert-Butyl-cyclohexanol was obtained by distillation of the clearfiltrate in 98% yield. The isomeric content was 81.9% of the cis isomerand 15.9% of the trans isomer.

EXAMPLES 2-5

A mixture composed of 86.72 g of 4-tert-butyl-phenol (0.578 mole), 2.31g of 5% by weight rhodium on alumina [equivalent to 1.12 mmole ofrhodium], 2.50 ml of tetrafluoroboric acid in a 31% solution [equivalentto 11.4 mmole of HBF₄ ] and 200 ml of tetrahydrofuran were introduced inan autoclave equipped with a stirrer under nitrogen, then hydrogen wasintroduced until the pressure settled down at around 5×10⁵ Pa.

The mixture was kept under vigorous stirring for about 24 hours at roomtemperature.

After filtering and the usual concentration work-up,4-tert-butyl-cyclohexanol was obtained in almost quantitative yield. Thecis/trans isomeric ratio was 84.1/15.9.

Other experiments were carried out according to the general proceduredescribed above and replacing HBF₄ by the complexes indicatedhereinafter. Facing the catalytic complex used is indicated thecis/trans isomeric ratio of the obtained 4-tert-butyl-cyclohexanol.

    ______________________________________                                                                     Isomeric ratio                                   Example   Catalyst           cis/trans                                        ______________________________________                                        3         Rh/Al.sub.2 O.sub.3 + BF.sub.3.2CH.sub.3 CO.sub.2 H                                              81/19                                            4         Rh/Al.sub.2 O.sub.3 + BF.sub.3.H.sub.3 PO.sub.4                                                  85/13                                            5         Rh/Al.sub.2 O.sub.3 + BF.sub.3.2H.sub.2 O                                                        81/18                                            ______________________________________                                    

EXAMPLE 6 Preparation of 4-tert-butyl-cyclohexanol

A mixture composed of 100 g (0.649 mole) of 4-tert-butyl-cyclohexanone,1.35 g of the catalyst prepared as indicated in Example 1 and 150 g ofcyclohexane were put into an autoclave under nitrogen and then hydrogenwas introduced until the pressure settled at about 10⁶ Pa. The mixturewas then heated to 70° and the reaction was followed by gaschromatography. The reaction was stopped by cooling and the autoclavewas flushed with nitrogen. After filtering, the catalyst was recoveredunder argon flow, washed with cyclohexane and recycled for the followinghydrogenation operations. The clear filtrate was evaporated to give aresidue that, once distilled, provided 95.15 g of an isomeric mixturecontaining 87.7% of cis isomer.

EXAMPLE 7 Preparation of 4-tert-butyl-cyclohexanol

By treatment of 50 g of 4-tert-butyl-phenol in the presence of 1.35 g ofthe catalyst prepared according to the process described above inExample 1B and carrying out the reaction as indicated in Example 1, amixture of 4-tert-butyl-cyclohexanol having a content in cis isomer of82.9% was obtained.

EXAMPLE 8 Catalyst recycling (lifetime) experiments

2 kg (13,33 mole) of 4-tert-butyl-phenol, 2 kg of cyclohexane and 28 gof the catalyst prepared as indicated in Example 1A were placed in anautoclave which had been purged 3 times with nitrogen. Hydrogen was thenintroduced until the pressure settled down at 16×10⁵ Pa. The reactionwas followed by GC and stopped when the conversion indicated a contentin intermediate 4-tert-butyl-cyclohexanone of 1% or lower. The reactionmixture was then treated as described in the preceding examples. Thecatalyst isolated by filtration was used in successive reactions asindicated in the following Table.

    ______________________________________                                                Reaction time                                                         Reaction n°                                                                    (hours)    % cis-Alcohol                                                                              % trans-Alcohol                               ______________________________________                                        1       1.8        84.7         14.5                                          2       2.0        84.0         15.5                                          3       2.3        83.8         15.4                                          4       3.0        83.8         15.6                                          5       3.0        83.1         15.8                                          6       2.5        83.2         15.8                                          7       2.8        83.9         15.3                                          8       3.0        82.1         15.0                                                  Average    83.6 ± .8 15.4 ± .4                                  ______________________________________                                    

What I claim is:
 1. A process for the preparation of4-tert-butyl-cyclohexanol, predominantly in the form of its cis isomer,which comprises hydrogenating 4-tert-butyl-cyclohexanone in the presenceof a catalytic system comprising rhodium on a suitable support, incombination with HBF₄ or BF₃.[Y]_(n) wherein Y designates a R₂ O group,R being a C₁ to C₆ lower alkyl radical, or a CH₃ CO₂ H,H₃ PO₄ or H₂ Ogroup and n is equal to zero, 1 or 2, at an effective temperature andpressure to prepare 4-tert-butyl-cyclohexanol.
 2. The process of claim 1which further comprises selecting the support to be one of Al₂ O₃, SiO₂,TiO₂, SiO₂.Al₂ O₃ or charcoal.
 3. The process of claim 1, wherein thecatalytic system is formed of Rh/Al₂ O₃.BF₃.
 4. The process of claim 1,wherein the ratio between the respective proportions of BF₃ and rhodium,expressed in molar quantities, is about 0.5 to
 15. 5. The process ofclaim 4 wherein the BF₃ : rhodium molar ratio is from 0.5 to
 5. 6. Theprocess of claim 1, wherein the hydrogenation is carried out at apressure of between 3×10⁵ and 2×10⁶ Pa and a temperature between 25° and200° C.
 7. The process of claim 6, wherein a temperature from 40° to130° C. is used.
 8. The process of claim 1, wherein the molar quantityof rhodium, relative to the molar quantity of starting4-tert-butyl-cyclohexanone ranges from 0.01 to 0.5%.
 9. The process ofclaim 1, wherein the hydrogenation is carried out in an organic solventwhich is inert under the reaction conditions.
 10. The process of claim8, wherein the hydrogenation is carried out in cyclohexane.
 11. Theprocess of claim 1 wherein the cis isomer is present in an amount of atleast 81.9%.